**2. N-acyl homoserine lactones mediated quorum sensing inhibition**

Quorum sensing (QS) is a system where bacterial cells communicate through the activation of specific signals, with key objective of enabling the adaptation of bacteria hostile environmental conditions, including bacterial population densities. This process involves reacting to extracellular chemical signaling molecules called autoinducers (AIs) through synthetization and sensing. Gram-negative bacteria communicate using AIs, most commonly acyl-homoserine lactones (AHLs) and other small molecules [14]. The mechanism is the disruption of AIs and then mitigate quorum sensing controlled responses for biofilm control. Most of the anti-biofilm chemical structures under studies are: N-acyl homoserine lactones (AHL) (**Figure 2a**), triazole dihydro furanone (**Figure 2b**), synthetic halogenated furanone (**Figure 2c**), EGCG (**Figure 2d**), and ellagic acid (**Figure 2e**) [14]. Numerous AHLs disrupt biofilm formation. Important biofilm inhibitory effect against *P. aeruginosa* and *Serratia marcescens* were observed when the lactone moiety of the native AHL molecules is replaced by cyclohexanone or cyclopentyl [15, 16].

### **3. Membrane permeabilization and potential alteration**

Pore formation and destruction of the cytoplasmic membrane is as a result of bacterial membrane modification. There are three possible mechanisms of bacterial membrane disruption by antimicrobial peptides (AMPs): (a) pore-induced barrelstave pathway, (b) toroidal pathway, and (c) carpet (non-pore) mode (**Figure 3**) [17]. Peptides that inhibit bacteria by disrupting their membranes and consequently inhibiting enzyme production are produced and post-translationally modified. These peptides are lantibiotics that are ring-structured peptide antibiotics containing thioether amino acids (methyllanthionine or lanthionine) or unsaturated amino acids (2-amino isobutyric acids or dehydro-alanine) [18]. A pore-forming lantibiotic called subtilin, produced from a Gram-positive bacteria *B. subtilis* strain ATCC6633, induces the dissipation of transmembrane electrostatic-potential releasing cytoplasmic solutes from *B. subtilis* and *Staphylococcus simulans* membrane vesicles [19]. In **Figure 2**, AMP outreaches the cytoplasmic membrane via permeabilizing the outer membrane in Gram-negative bacteria,

#### **Figure 2.**

*Chemical structures of some anti-biofilm compounds that inhibit AHL-mediated QS. (a) AHL. (b) Triazole dihydro furanone. (c) Synthetic halogenated furanone. (d) Epigallocatechin gallate (EGCG). (e) Ellagic acid.*

#### **Figure 3.**

*Mechanism of action of AMPs on the membrane system of Gram-negative and Gram-positive bacteria [17].*

while in Gram-positive bacteria, the AMP directly disperses through nano-ranged pores of the peptidoglycan layer. After binding to the inner membrane, AMPs can create three types of pores, that is, barrel-stave pore, toroidal pore, and carpet model [17].

## **4. Peptidoglycan cleavage**

Peptidoglycan, the cleavage of which is also known to inhibit biofilm formation, is a layer located in the cell walls of many bacteria and originates from amino acids

*Bacterial Biofilm Eradication in Human Infections DOI: http://dx.doi.org/10.5772/intechopen.113341*

and sugars [20]. Peptidoglycan cleavage causes a change in protein composition and amount of teichoic acid in the bacterial cell wall resulting to biofilm inhibition [20]. An example of peptidoglycan hydrolases is endolysin encoded by bacteriophages [21]. Endolysin can work on multidrug-resistant strains, by disrupting biofilms *in vitro* e.g., PlyC (specific Streptococcal bacteriophage) [22].
